1. Field of the Invention
The invention relates to a device for handling liquid samples, a system for handling liquid samples, and a process for the manufacture of the device.
2. Description of the Prior Art
The handling of liquid samples or “sample handling” specifically comprises the proportioning (e.g. the pipetting, dispensing, loading of microtitration plates and gel electrophoretic plates), the transporting, centrifuging, tempering, and mixing of the samples, the closing (especially that of cells), cleaning, filtration, and concentration, the reaction of samples and/or reagents, and the measurement (especially the fluorimetric and photometric measurement) of samples.
The applicant has made known a system for handling liquid samples which comprises a multiplicity of various disposables (expendable articles which are discarded after a single or multiple use) and devices. This system is referred to as a “microtitration system” because the sample receptacles of the disposables have volumes in the range of some tenths to some thousandths of microliters. It comprises the following fields:                Proportioning of volumes between 0.2 and 5,000 microliters using pipette tips or syringes along with appropriate proportioning devices,        Sample transport, centrifuging, tempering, and mixing using reaction vessels for volumes of from 0.2 to 2.0 ml along with appropriate devices,        Measuring equipment based on cuvettes and fluorimeters, luminometers, and photometers, and        Cell manipulation (e.g. cell fusion, cell poration, and cell positioning) which is particularly based on cuvettes.        
However, more and more smaller volumes and more and more higher spatial densifications of the volumes are used at an increasing tendency in all fields in the medical, biological or chemical laboratories. Since the end of the 80-ties, the microtitration plate which comprises a multiplicity of sample receptacles in the form of indentations lined up in rows next to each other has pushed its way instead of using individual reaction vessels, particularly in immunological analytics. As a result, the existing proportioning systems (e.g. the microliter pipette) were further improved to form multi-channel proportioning systems.
Initially, microtitration plates having 96 receptacles (“wells”) were used in a 9 mm grid. Nowadays, it is particularly the methods for DNA multiplication (PCR) and for a DNA analysis which more and more frequently require working on a large number of samples in a highly parallel way. Thus, in the middle of the 90-ties, microtitration plates have become known which have 384 wells in a 4.5 mm grid measure. Microtitration plates having 1,536 wells in a 2.25 mm grid measure already exist meanwhile. These and further spatial densifications of the sample wells are expected to be more and more successful.
However, the development of the proportioning and vessel systems did not keep pace with the above described development. Multi-channel pipetting devices working with a multiplicity of pipette tips will meet the need to densify wells in microtitration plates only to a limited extent.
The manufacture of “gel loaders” also relies on pipette tips. For instance, pipette tips are stretched in an expensive second operation so as to form a thin gel loader tip or are flattened by pressure to have a thickness of 0.2 to 0.4 mm in order that they may be introduced into the narrow space between gel electrophoretic plates. These technologies do not allow high-degree parallelization and do not open up a possible way to reducing the dimensions with a view to reducing the grid measure for gels.
DE 198 43 691 A1 has made known a strip of tips comprising a number of interconnected pipette tips which are substantially disposed in parallel and are located side by side. The tips are hollow and each tip consists of a tip body and a flattened distal end. The flattened ends are substantially disposed in a plane in a coplanar manner, thus permitting the flattened ends to be introduced between tightly arranged plate surfaces of gel electrophoretic plates. Limits are also set to the spatial densification of this strip of tips which is intended to be manufactured from plastic, particularly by injection moulding.
The technology of integrating filtration elements into proportioning and vessel systems involves technical expenditure and is hardly suited for any further spatial densification. For instance, such filtration elements may serve as pipette tips to protect them from cross-contamination by aerosols or as filter inserts in reaction vessels or for bacteria cultures in membrane vessels or for microdialysis.
There is no integrated technical solution to enlarging the reaction surfaces for reaction vessels and pipette tips. As a rule, the insertion of cartridges and “columns” is resorted to which, via membranes or glass frits, communicate with the volume to be reacted.
Therefore, it is the object of the invention to provide a system for handling liquid samples and a process for the manufacture of the device for handling liquid samples, particularly for sample volumes of about 0.001 microliters and greater. It should be possible here to arrange such devices side by side at very short distances. Further, the devices should be adapted to be designed as disposables.